Salusins are regulatory peptides that affect cardiovascular function. We previously reported that salusin-a and -β protected cultured cardiomyocytes from serum deprivation-induced cell death through upregulating gluc...Salusins are regulatory peptides that affect cardiovascular function. We previously reported that salusin-a and -β protected cultured cardiomyocytes from serum deprivation-induced cell death through upregulating glucose-regulated protein 78 （GRP78）, an endoplasmic reticulum （ER） resident protein whose overexpression acts as a marker and suppressor of ER stress. The present study examined whether salusin-α and -β inhibit ER stress in ischemic myocardium. In a rat model of myocardial infarction created by ligating the left anterior descending coronary artery （LAD）, salusin-α or -β was intravenously injected at 5 or 15 nmol kg-1 15 min prior to 2 h of LAD occlusion. The high dose of salusin-α and -β3 significantly improved heart function and hemodynamics in LAD-occluded rats, but had no effects in sham-operated rats. The arrhythmias caused by LAD oc- clusion were markedly attenuated by salusin-α and -β. The apoptotic rate in ischemic myocardium was reduced from 31.5%±3.7% to 19.8%±2.2% and 12.3%±2.2%, and the infarct size was reduced from 53.4%±4.0% of the risk area to 26.5%±9.7% and 23.7%±8.9% by 15 nmol kg-1 salusin-α and -β, respectively. Furthermore, salusin-α and -β prevented the ac- tivation of GRP78 and ER stress-specific apoptotic effectors caspase-12 and CHOP （C/EBP homologous protein）, and attenu- ated the reduction of an ER stress-associated antiapoptotic protein Bcl-2 in ischemic cardiac tissue. The salusins also inhibited the ER stress induced by tunicamycin in cultured rat H9c2 cardiomyocytes. These results indicate that salusins protect myo- cardium against ischemic injury by inhibiting ER stress and ER stress-associated apoptosis.展开更多
基金supported by the National Basic Research Program of China (Grant Nos. 2006CB503807 and 2009CB521902)the National Natural Science Foundation of China (Grant Nos. 30600763, 30870906, and 31071023)+2 种基金the Pujiang Project of Shanghai, China (Grant No.08PJ14001)the Project Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education of China (Grant No. [2008]891)the Fund for Outstanding Young Teachers in Higher Education Institutions of Shanghai, China (Grant No.[2009]63)
文摘Salusins are regulatory peptides that affect cardiovascular function. We previously reported that salusin-a and -β protected cultured cardiomyocytes from serum deprivation-induced cell death through upregulating glucose-regulated protein 78 （GRP78）, an endoplasmic reticulum （ER） resident protein whose overexpression acts as a marker and suppressor of ER stress. The present study examined whether salusin-α and -β inhibit ER stress in ischemic myocardium. In a rat model of myocardial infarction created by ligating the left anterior descending coronary artery （LAD）, salusin-α or -β was intravenously injected at 5 or 15 nmol kg-1 15 min prior to 2 h of LAD occlusion. The high dose of salusin-α and -β3 significantly improved heart function and hemodynamics in LAD-occluded rats, but had no effects in sham-operated rats. The arrhythmias caused by LAD oc- clusion were markedly attenuated by salusin-α and -β. The apoptotic rate in ischemic myocardium was reduced from 31.5%±3.7% to 19.8%±2.2% and 12.3%±2.2%, and the infarct size was reduced from 53.4%±4.0% of the risk area to 26.5%±9.7% and 23.7%±8.9% by 15 nmol kg-1 salusin-α and -β, respectively. Furthermore, salusin-α and -β prevented the ac- tivation of GRP78 and ER stress-specific apoptotic effectors caspase-12 and CHOP （C/EBP homologous protein）, and attenu- ated the reduction of an ER stress-associated antiapoptotic protein Bcl-2 in ischemic cardiac tissue. The salusins also inhibited the ER stress induced by tunicamycin in cultured rat H9c2 cardiomyocytes. These results indicate that salusins protect myo- cardium against ischemic injury by inhibiting ER stress and ER stress-associated apoptosis.
